# Cell free nucleic acid-based biomarkers in advanced prostate cancer

> **NIH NIH R01** · H. LEE MOFFITT CANCER CTR & RES INST · 2021 · $594,224

## Abstract

PROJECT SUMMARY
Metastatic hormone-sensitive prostate cancer is treated with androgen deprivation therapy and after progression
to the castration-resistant prostate cancer stage, with additional forms of hormonal ablation and/or with
chemotherapy. These treatments slow tumor progression by a certain period and decrease the pain and
suffering from disease progression. However, there is no clinical feature or molecular test that can reliably predict
these treatment responses or clinical outcomes in advanced prostate cancer. A predictive feature or biomarker
which is defined as a factor determining which patients will do well with a specific type of treatment. This is
distinct from molecular prognostic biomarkers which provide information about clinical outcome regardless of
therapy used. Knowledge of predictive factors that identify cohorts of patients destined for response (versus
failure) of these therapies is critically needed to develop precision medicine strategies. Recently, the assessment
of tumor-derived cell free nucleic acids in body fluids has shown promise in being able to capture tumor genomic
and genetic abnormalities in cancer patients. This approach is often referred to as “liquid biopsy”. We believe
that cell free nucleic acids can be used as biomarkers to reliably predict treatment response and clinical
outcomes, and will therefore be informative in designing an appropriate treatment regimen. We have previously
examined plasma cell free nucleic acids for miRNA abundance and somatic DNA changes in patients with
advanced prostate cancer. We observed a significant association of high plasma miRNAs (miR-375 and miR-
1290) with poor overall survival. We also observed that tumor-derived genomic/genetic alterations in plasma cell
free DNAs were associated with tumor burden and reflected patients' responses to stage-specific treatments.
Aim 1 of this study is to identify and validate key circulating miRNA-based predictive and prognostic biomarkers
in four well annotated prostate cancer cohorts. Aim 2 is to establish circulating cell free DNA-based predictive
and prognostic biomarkers in four well annotated prostate cancer cohorts. Aim 3 is to functionally characterize
the potential of the key candidate miRNAs in promoting growth and resistance of prostate cancer cells to
androgen deprivation therapy or chemotherapy in vitro and in vivo. The proposed studies are highly significant
and timely, as the circulating cell free nucleic acid-based biomarkers will not only help clinicians in selecting the
most effective treatment options, but also provide important clues regarding mechanisms that underlie prostate
cancer progression and recurrence.

## Key facts

- **NIH application ID:** 10240337
- **Project number:** 5R01CA212097-05
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Manish Kohli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $594,224
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240337

## Citation

> US National Institutes of Health, RePORTER application 10240337, Cell free nucleic acid-based biomarkers in advanced prostate cancer (5R01CA212097-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10240337. Licensed CC0.

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